Novel Methods for Clinical Trials in Dementia and Cognitive Decline

摘要： 我们将进行一项开放标签双盲分组临床试验，检测血清“脂肪因子”蛋白 作为联邦药物管理局（FDA）批准的药物多奈哌齐（Aricept®）的作用的介质 潜在性痴呆严重程度指标“δ"的影响脂肪因子是由脂肪组织释放的炎症蛋白 最近与认知能力下降有关。我们的目的是展示多个潜在的改进， 任何未来痴呆症相关临床试验的开展。例如，使用电话评估 最大限度地减少招募和评估成本，保护参与者免受潜在的SARS-cov-2暴露。 如有必要，整个方案可通过电话在未接种抗 SARS冠状病毒2型在先前的工作中，我们已经建立了潜在变量“δ”（痴呆症）作为痴呆症特异性 认知表型我们将使用δ来等同研究组的基线痴呆严重程度， 招募阈值，以最大限度地提高δ痴呆转换阈值的逆转潜力 如果治疗有效。我们将部署一种新的“身份线（LOI）”算法，以进一步选择最多的情况 可能从我们的干预中受益（精准医疗的一个例子）。我们将使用第二个潜伏的 痴呆严重程度度量（dTEL）作为一个全面的痴呆特异性结果。最后，我们将测试一个潜在的 脂肪因子生物标志物构建体作为多奈哌齐对δ.这可能会成为一部小说 乙酰胆碱酯酶抑制机制。

Abstract: We will conduct an open-label double-blind group assignment clinical trial testing serum “adipokine” proteins as the mediators of the Federal Drug Administration (FDA)-approved medication donepezil (Aricept®)’s effect on the latent dementia severity metric “δ”. Adipokines are inflammatory proteins released by adipose tissues and recently associated with cognitive decline. Our intent is to demonstrate multiple potential improvements in the conduct of any future dementia-related clinical trial. For example, the use of telephone assessment minimizes recruitment and assessment costs and protects participants from potential SARS-cov-2 exposure. The entire protocol could be administered by telephone, if necessary, in subjects unvaccinated against SARS-cov-2. In prior work, we have established the latent variable “δ” (for dementia) as a dementia-specific cognitive phenotype. We will use δ to equate study groups on their baseline dementia severity and set the recruitment threshold to maximize the potential for reversions back across δ’s dementia conversion threshold if treatment is effective. We will deploy a novel “Line of identity (LOI)” algorithm to further select cases most likely to benefit from our intervention (an example of precision medicine). We will use a second latent dementia severity metric (dTEL) as a comprehensive dementia-specific outcome. Finally, we will test a latent adipokine biomarker construct as a mediator of donepezil’s effect on δ. That will potentially establish a novel mechanism for acetylcholinesterase inhibition.